MicroRNA-92a在胰腺癌中的表达及对肿瘤生长的影响

Effect of MicroRNA-92a on pancreatic ductal adenocarcinoma

目的探讨人胰腺导管腺癌(PDAC)中microRNA-92a(miR-92a)的表达及对肿瘤细胞生长的影响。方法实时荧光定量聚合酶链反应(qRT-PCR)检测PDAC组织中miR-92a的表达水平;慢病毒转染PANC-1细胞构建miR-92a稳定敲除模型,克隆形成与流式细胞仪检测细胞增殖凋亡;通过裸鼠皮下种植瘤模型检测下调miR-92a表达对肿瘤体内生长的影响;PCR及Western blotting检测miR-92a下游靶点DOC-2/DAB2结合蛋白(DAB2IP)在体外培养细胞中的表达水平;免疫组织化学检测DAB2IP在移植瘤组织中的表达水平。结果 miR-92a在PDAC组织中表达水平高于癌旁组织(P <0.05);miR-92a高表达的胰PDAC者肿瘤体积较miR-92a低表达者更大(P <0.05);下调miR-92a的表达能够抑制胰腺癌PANC-1细胞体外增殖能力,促进细胞凋亡,并抑制PANC-1细胞裸鼠皮下种植瘤的生长;下调miR-92a表达提高了PANC-1细胞内DAB2IP的表达水平及移植瘤组织内DAB2IP的表达水平(P <0.05)。结论 miR-92a在胰腺癌中表达升高,下调miR-92a的表达能使DAB2IP的表达下调而发挥抗肿瘤生长作用。

Objective To investigate the expression and effect of MicroRNA-92 a on pancreatic ductal adenocarcinoma(PDAC).Methods The expression of MicroRNA-92 a in PDAC was detected by qRT-PCR.MicroRNA-92 a inhibitory lentivirus was utilized for establishment of MicroRNA-92 a knockdown model in PANC-1 cells.Clone formation assay and flow cytometry were performed for cell proliferation and apoptosis.A subcutaneous xenotransplanted tumor model was conducted to investigate the effect of MicroRNA-92 a on tumor growth in vivo.Expression of DAB2 IP and MicroRNA-92 a in mice tumor tissues were identified by Western blots or immunohistochemical(IHC).Results MicroRNA-92 a was up-regulated in PDAC tissues(P<0.05).Knockdown of MicroRNA-92 a suppressed cellular proliferation(P<0.05) while enhanced apoptosis rate(t =5.840,P = 0.029) in PANC-1 cells.Down-regulation of MicroRNA-92 a inhibited in vivo tumor growth(P<0.05).Moreover,deletion of MicroRNA-92 a induced increased expression of DAB2 IP in vitro(P<0.05) and in vivo(P<0.05).ConclusionsMicroRNA-92 a facilitates PDAC tumor growth probably through activating DAB2 IP.